The Cleveland Clinic: 2004 Medical Innovation Summit Part I

Strategic Alliance Partnership | <b>Cleveland Clinic</b>

On October 18-20, 2004, hundreds of top-level executives from the medical device, biotech, and pharmaceutical industries, entrepreneurs and investors from all across the globe, and thought leaders...

On October 18-20, 2004, hundreds of top-level executives from the medical device, biotech, and pharmaceutical industries, entrepreneurs and investors from all across the globe, and thought leaders and other clinicians representing medicine’s best and brightest gathered in Cleveland, Ohio to attend what has been called a “national medical innovation summit.”

For the second year in a row, the InterContinental Hotel and MBNA Conference Center on the main campus of The Cleveland Clinic played host to a unique event that addressed the changing environment in which breakthroughs in medicine and science are conceived, tested, nurtured, financed, and shepherded to market, where they ultimately find their way into the hands of the practitioners in the trenches. This year’s Summit placed particular emphasis on challenges in cardiovascular medicine and touched on themes that included:

The evolving regulatory arena

New clinical approaches to familiar problems

Gene and cell-based therapies

The effects of an “uncertain environment” on innovation

State-of-the-art developments in cardiothoracic surgery, touching on both new technologies and new techniques and interventions

The economic tensions that underlay innovation and commercialization

And, of course, how to pay for it all

Attendees were treated to cutting-edge lectures and presentations in a state-of-the-art facility. The lofty goals and subject matter of the Summit were perhaps matched only by the rarefied status of many of the key speakers and panel participants. If you didn’t make it to this year’s Summit, you missed:

• Amgen Chairman and CEO Kevin Sharer explaining the keys to his company’s success

• Boston Scientific Chairman and CEO James R. Tobin talking about the insight earned during the long process that lead to the development of one of his company’s greatest breakthroughs

• Cordis President Guy Lebeau, MD, revealing the issues biotech companies must address in order to accelerate innovation in an uncertain environment

• Chairman of the Cleveland Clinic Department of Thoracic and Cardiovascular Surgery Bruce Lytle, MD, holding forth on the future of cardiovascular surgery

• Acting FDA Commissioner Lester M. Crawford, DVM, PhD, outlining his vision for far-reaching reforms at the country’s top regulatory body

• Biotechonomy Chairman and CEO Juan Enriquez regaling the audience with tales of life on the ramparts of the genomic revolution

• And much more

MD Net Guide was there to cover the proceedings; this special supplement features summaries of nearly every Summit presentation, complete with bulleted highlights, memorable quotes, and supplemental interviews with several speakers. Nearly every presentation from the Cleveland Clinic 2004 Medical Innovation Summit is available for viewing online; where possible, we have included a link and viewing instructions with each summary.

We also interviewed Chris Coburn, executive director of CCF Innovations, an organization responsible for moving the inventions of the Cleveland Clinic into the private marketplace. Mr. Coburn served as the de facto master of ceremonies during the Summit and was instrumental in organizing the event. We wanted to get his thoughts on the success of the Summit, and what the medical community can expect in the future.

MDNG: Why is the focus of the Summit important not just for investors and the corporate sector, but also for physicians?

CC: We conceived the Summit as a unique venue where investors, executives, and physicians can learn about the latest technology from an innovation standpoint, but do it in a clinical setting. The Summit brings together a large number of CEOs, venture capitalists, and top MDs in a unique setting. It’s a chance to hear what the CEOs of, in the case of this past Summit, Boston Scientific or Guidant have to say about upcoming market challenges. But at the same time, you can hear Bruce Lytle or Eric Topol talk about what’s going on in cardiology or cardiac surgery.

MDNG: Would you consider this year’s Summit a success?

CC: Absolutely. After the meeting, we received an amazing amount of enthusiastic correspondence; participants enthused how great the Summit was, how well organized it was. The concensus was that it was better than last year—and most of these people thought that wasn’t possible. We’re very excited; we actually have already had several meetings to shape the agenda for the 2005 Summit.

MDNG: How is that progressing? What key themes are emerging?

CC: Our proposition right now is that we will have the same structure; we’re talking about innovation from bench to boardroom to bedside. Next time the focus will almost certainly be orthopedics. We’ll also do an update on developments in cardiovascular medicine over the past year.

MDNG: What key insights did you take away from this version of the Summit?

CC: I would say the most important one is—and we picked this up after the first year—people told us they wanted to know what Cleveland Clinic MDs were thinking. That was clear both at the first meeting and also in the survey work. Looking at the program, I think we had a dozen or more of our senior MDs ranging from cardiologist to cardiac surgeons to vascular surgeons, and we got rave reviews. By coming to this conference, you get a chance to hear a dozen speakers who are all leaders in their field and you have a chance to interact with them. It’s a very powerful tool.

MDNG: How do you see the pharmaceutical and device development environment changing in the next five years? What can the physicians on the front lines expect see in the near future?

CC: Let me try to give a couple answers. You’re going to have continuing fusion between drugs and devices, and that fusion will bring its own set of challenges, whether they’re regulatory or reimbursement-related or framed in terms of market acceptance. We’ve already seen the beginnings os this transformation, but clearly we’ll see more in the future. I think, big picture, you’re going to see an acceleration of acquisition by large companies, whether its drug or device, of smaller companies as the hunt for ever more effective therapies and diagnostics becomes more pressing. I think there will be a strong cost element to the consideration of any new drug or any new introduction. And there seems to be still some continuing debate on personalized medicine: whether or not it will be a net cost saving or cost expense. I think there will be more insistence on having cost discussion be part of the technology development. There will be more economic drivers.

MDNG: Do you feel a lecture setting with Q & A is the best atmosphere for these people to learn and also to influence their behavior?

CC: That’s a great question. What’s the right pedagogy or approach for what we’re trying to achieve is something we constantly ask ourselves. I think the lecture format works well when you think of (Boston Scientific Chairman and CEO) Jim Tobin and how he was able to connect with the audience and share insights. I think you wouldn’t want that exclusively as your design, so that’s why we feature the panels and the live surgery. I think the weaving of those approaches together is very important and is what makes this Summit so successful.

I think we’ve established a franchise that physicians, investors, and executives think is both important and valuable, and we’re committed to building from that in the future. If people have suggestions, we are very open to them. We want to get back out to people with a pretty clear program design and dates for 2005 by the end of this year.

The Amgen Experience — Industrial Innovation: A Laborer’s ViewKevin Sharer, Chairman and CEO, AMGEN

“For the idea, technology, or thing to actually become useful, it must be industrialized; industrialized means a whole panoply of things to get the idea from the lab into the clinic or into the hands of the user.”

Overview:

Drawing from his day-to-day and his company’s approximately 25-year experience—as an enterprise that spends $2 billion/ year on R&D and has many products under development, seven drugs on the market (five making more than $1 billion/year), 14,000 staff, a broad and unmatched technology base, aggressive outreach, nearly 1,500 scientists and doctors in laboratories and clinics, and an unusual degree of CEO and BOD support and involvement—Sharer offered some general lessons learned in medical innovation.

Key Points:

• “For the idea, technology, or thing to actually become useful, it must be industrialized; industrialized means a whole panoply of things to get the idea from the lab into the clinic or into the hands of the user.”

• Managing the pipeline—taking an idea from the laboratory through the FDA into the market—is the most complicated industrial management task. “You have to do about 20 different things simultaneously well, and then you have to be a bit lucky. To do any of the 20 is not easy, and to do all simultaneously is extraordinarily difficult.”

• Innovation is fostered by critical drivers at multiple levels: There must be people who have an innovative, risk-taking mindset, and there must be critical mass. Also, the firm itself plays a key role; the CEO must give special guidance and nurturing, the firm’s culture must be one of innovation, the person in charge of R&D must encourage much dialogue and talent and be willing to sometimes be wrong (if this isn’t the right person, all other 19 items needed for innovation don’t matter).

• The industry itself is a key driver; it must have an R&D bias, a technology base, include companies that make enough for investment, have an innovation flow (from the lab to the small company to the big company), a degree of competitiveness, and financial rewards for success

• Another key driver is the national environment, which needs to have regulation plus legislation, provide political support, include investment by government and the industry, host a good educational system, allow for a large market, and, very importantly, provide an opportunity for a return on capital for successful entrepreneurs. According to Mr. Sharer, when taking these requirements into account, there is an enormous advantage in the US.

• The biotechnology industry is no longer just a boutique. Although most companies don’t make any money, they’re making a significant contribution to the system, with $18 billion spent on R&D and $39 billion total revenue in 2003.

• Of all drugs approved in 2003, 39% were biotechnological, up from 25% in 2001 and 13% in 1999. Says Mr. Sharer: “We’re here to stay.”

• Amgen “does not invent to market, we market our inventions.”

• With a concentration on grievous illness, Amgen has the idea that “we don’t have to fit the target to our modality. We fit the modality to the target.” This is a very important advantage in the biopharmaceutical world.

• Keys to Amgen’s success include a decisive, flexible, and value-based culture; a pervasive outreach; investing as much as it can in R&D; remaining fact-based, open, and fast; visible and constant CEO support; a broad-based and evolving technology base; and an attitude that there is no substitute for the best people.

• Innovation is required everywhere, in clinical trial design (can’t have anything without them), manufacturing, reimbursement (it’s not enough that it works, you need to prove that it’s better than the rest and “worth it”), FDA approval, and competition.

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James Tobin, CEO, Boston Scientific

TAXUS: How Did We Get So Lucky? The Harder We Worked, the Luckier We Got

“Most device companies do just enough trials to get a product approved, and let nature take its course...We got the end results we wanted, we got the product approved, but we didn’t stop there.”

Overview:

Mr. Tobin discussed the long, arduous process that led to the development of the TAXUS Express paclitaxel-eluting coronary stent system, a groundbreaking product that combines a proven stent, reliable polymer, and effective drug to offer patients “the ability to reduce restenosis, treat a variety of lesions, and achieve safe [and] predictable outcomes.” He drew upon his own experiences at Boston Scientific to illustrate the importance of employing the right approach when manufacturing a product, from the first steps right down to its culmination.

Key Points:

• “It took us years to get to the point where we had a stent that we could actually think about coating. From the very beginning, Boston Scientific perceived it as a drug delivery problem, as opposed to a drug molecule problem.”

• Roughly 80 companies worldwide produce stents, nine develop a drug-coated stent, and two received approval. Boston Scientific became one of the elite two by finding the right drug, the right polymer, the right dose, and the right duration.

• In 1997, Boston Scientific made a deal with Angiotech Pharmaceuticals, Inc. to use paclitaxel, a drug that was shown to have many ancillary advantages, and more importantly, was proven safe and effective for this application. Boston Scientific was “lucky” in the respect that the first drug they tried was one that worked.

• “The polymer has to be stable, it has to be compatible with the drug, it has to be non-inflammatory, it has to be sterilizable, and it has to be expandable. At the end of the day, it’s actually a lot harder to find a polymer that works than a drug that works.” The polymer that worked the best and had all the desired properties was Translute, which had been sitting on Boston Scientific’s shelf.

• Boston Scientific initiated TAXUS I using 60 patients, 30 of whom took paclitaxel, then soon launched TAXUS II, a dose escalation trial that proved the slow-release version worked.

• A biotech approach was used in the clinical trials, which entailed having some capability within the company to design the trials, but also using experts on the outside to help. Another key was that Boston Scientific insisted on running the trials with the best doctors it could find, not just friends of Boston Scientific.

• In TAXUS V and VI, Boston Scientific tested the stent in real-world situations, as opposed to the “stylized, carefully-designed” pivotal trials that are much more typical, and insisted on using as many patients as possible in the trials.

• The coated stent that became TAXUS was found to be safe, effective, and manufacturable. “It fit our strategy of a minimum effective dose. Slow release and moderate release pretty much got us the same results. So why would you use more drugs if you could use less? That’s the way we went at it.”

• Boston Scientific has spent more than $600 million on TAXUS and will continue to spend. “Most device companies are just not equipped from a regulatory point of view to be able to handle that. It comes down to people.”

• “TAXUS really is a combination product…You have to sell it like a device, but you have to make development decisions like a drug company.”

• “The bottom line is, we got lucky, no question about it, but the harder we worked, the luckier we got. And the key to the whole thing was focus, focus, focus.”

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Cardiovascular Innovation in Action

Panel Moderated by Eric J. Topol, MDProvost and Chief Academic Officer, and Chairman, Cardiovascular Medicine, The Cleveland Clinic

Featuring: Marc S. Penn, MD, PhD, Patrick L. Whitlow, MD, Ferolyn Powell, CEO, Evalve, Bruce L. Willkoff, MD, Mario J. Garcia, MD

Overview:

Dr. Topol provided a brief assessment of the current state of cardiology in this introduction, in which he stressed the need for “smart medicine,” provided examples of technologies and clinical trials that exemplify this idea, identified instances in which “smart medicine” is not being practiced, and provided some valuable insights on what can be done to improve the state of cardiology.

Key Points:

• “We practice ‘dumb medicine’ today;” 10 million women without a cervix receive pap tests every year, which is “extremely costly and of no value whatsoever.” Studies are being performed to determine if dogs can detect cancer, yet drugs that “lack safety profile” and even “induce heart attacks” are being approved.

• There are 15 medications for heart disease and more than 178 for cancer, though cardiovascular medications have a success rate of 20% compared to 5% for oncology drugs.

• An example of dumb medicine: calcium score. An example of smart medicine: multi-slice CT or MRI.

• The concept of using chips to track the progress of patients using gene expression data as opposed to biopsies is “smart medicine.”

• Another example of smart medicine is seen in devices that can treat heart attacks 30 or 50 years before they happen by tracking mutations or deletions in particular genes that impair the gene’s ability “to perform its function in the nucleus.”

• “Medicine needs to undergo an extreme makeover. Hopefully, in the times ahead, we’ll be able to focus much more on getting away from just treatment and focus on prevention.”

Check out www.mdng.com for more with Dr. Topol.

Marc S. Penn, MD, PhD

Director, Cardiac Intensive Care Unit, and Cardiovascular Medicine Department’s Experimental Animal Laboratory, The Cleveland Clinic

Overview:

Dr. Penn, who has performed extensive research on the optimization of gene and stem cell therapies for the regeneration of myocardial tissue, provided insights on the potential role of stem cells in the prevention and treatment of heart failure (HF).

Key Points:

• “Mortality from heart disease has gone down substantially, but the cost of this has been the significant rise in the number of patients who suffer from congestive heart failure.”

• Patients older than age 65 now carry about a 10% prevalence of CHF.

• A controversial study using stem cells in mice showed improvements in heart function. Some experts argued that the “stem cells went into the heart, differentiated into cardiac myocytes, and improved heart function,” while others disagreed. Regardless, there was improvement in heart function.

• Totipotent embryonic stem cells “can become any organ system in our body.”

• Pluripotent umbilical cord stem cells “seem to have the ability to become many different lineages and can perhaps help function.”

• “The debate continues as to whether there is transdifferentiation—whether mesenchymal cells can become hematopoietic cells, and vice versa.”

• Injecting CD34 stem cells hasn’t shown to have significant benefits in patients who have had bypass surgery.

• “We are learning that there’s actually a natural, but inefficient stem cell-based repair process that attempts to repair the heart soon after a heart attack.”

• In the future, the clinical strategy for patients with CHF will consist of injected engineered cells in the heart.

• Issues that must still be addressed include stem cells for cardiac repair, differentiation factors, autologous versus allogeneic cell therapy, the arrhythmogenic risks of cell therapy, which patients need to be treated, and the issue of whether gene-based cell therapy is necessary.

Patrick L. Whitlow, MD

Director of Interventional Cardiology, The Cleveland Clinic

Overview:

In this brief summary of interventional cardiology, Dr. Whitlow reviewed the progress the cardiac cathartic lab has made during the last 40 years, and discussed several of the non-coronary procedures currently being performed.

Key Points:

• The cardiac cath lab has changed dramatically over the years, going from a diagnostic-based lab in the 60s and 70s, to a more therapeutic-based lab in the 80s with balloon dilation and atherectomy, to the 90s and into the present with drug-eluting stents.

• Once coronary-based, it now includes all cardiovascular diseases, including peripheral vascular disease.

• The non-coronary cath lab procedures being performed today include:

Quantitative/Qualitative plaque assessment

Vascular stenting with embolic protection

Abdominal aortic stent grafting

Septal ablation for hypertrophic cardiomyopathy

Pulmonic, mitral, aortic valvuloplasty

Closure of congenital heart defects(ASD and PFO)

Cell therapy for CHF (to restore blood flow and function)

Acute stroke intervention (for acute MI)

Stroke prevention

Protected carotid stenting

Percutaneous valve repair/replacement

Left atrial appendage obliteration

Ferolyn Powell

President and CEO, Evalve, Inc.

Overview:

In her presentation, Ms. Powell discussed the current focus of Evalve’s development efforts, the status of the Evalve percutaneous mitral valve repair system, which is currently in clinical trials, the impact that Evalve’s non-invasive procedures will have on both physicians and patients, the direction in which research and development is headed for Evalve, and more.

Visit www.mdng.com to read an interview with Ferolyn Powell for key points discussed during her presentation and more.

Bruce L. Willkoff, MD

Director of Cardiac Pacing and Tachyarrhythmia Devices, Medical Director of Clinical Electrophysiology Research, Department of Cardiology, The Cleveland Clinic

Overview:

Dr. Willkoff focused on the innovations in implantable devices and other technologies that the cardiac community will see in the near future and explained the implications of these innovations.

Key Points:

• Projected cardiac rhythm management (CRM) innovations in the next five years:

• Integration of imaging and device therapies

• Pericardial access/epicardial-based therapy

• Comorbidity management

• Remote connectivity disease progression management

• “Implantable devices provide information that we are blind to most of the time.” They allow us “the ability to take objective information transcutaneously through telemetry, send that information by Internet or by satellite, and integrate that information to the EMR database, providing feedback to the patient.

• This technology is “very broadly applicable. In the future, you’re going to see many technologies for infusing drugs and putting in leads.”

• “We can provide diagnostic and therapeutic functionality to enhance management of diseases that will allow physicians to “find out about blood pressure and glucose and potassium.”

• Censor technology allows us to track the progression of AF, HF, sleep apnea, hypertension, hypotension, ischemia, and diabetes.”

• Other technologies on the horizon that will enable effective disease progression management include: remote patient monitoring, high-speed telemetry, wireless telemetry, referring physician—patient communications devices, “smart” device-based patient alert, data integration to hospital-based EMR, MRI compatibility, and device therapy at a lower cost per day.

Mario J. Garcia, MD

Director of the Echocardiographic Laboratory, The Cleveland Clinic

Overview:

In this update of several innovations that he predicts will change the face of cardiovascular medicine, Dr. Garcia focused on the potential affects of echocardiography, ultrasound, and other imaging and tomography techniques and procedures.

Key Points:

• Real-time stress 3-D echocardiography is a technology that has the ability to “perform dedicated imaging in real time of the heart while guiding therapeutic devices.” It is also able to “deliver gene material at a precise location,”

• With ultrasound, “we can identify the patients who are more likely to improve after cardio resynchronization. I predict this is the way we will be performing patient selection in the future.”

• Ultrasound systems “provide the ability to perform diagnosis from remote locations, and with implementational telemedicine now, we can read ultrasound images from anywhere in the world.”

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Case Study in Cardiovascular Therapy

Roger S. Newton, PhD, CEO of Esperion Therapeutics

Steve Nissen, MD, Cardiology, Cleveland Clinic Foundation

“All the pieces fell into place. But it wasn’t by accident. Both groups had to make major accommodations in order to work together in a way that would bring a new therapy forward.” —Steve Nissen, MD

Overview:

Mr. Newton and Dr. Nissen discussed the successful collaboration between the biotech industry and academia to produce promising trial results for HDL therapy in the reduction of plaque volume within the coronaries.

Key Points:

• A genetic variant of a protein known as Apolipoprotein A-1 was discovered to make HDL more efficient at clearing excess cholesterol from arterial plaque and moving it to the liver for elimination.

• This discovery led to the development of a synthetic version of ApoA-1 Milano, which Esperion began producing recombinantly by splicing the gene into E. coli.

• In a 10-center study directed by the Cleveland Clinic, patients were infused with five doses of the synthetic HDL after a heart attack. Using a technique known as intravascular ultrasound, Dr. Nissen’s research team measured the plaque in the coronaries before and after five intravenous doses given at one-week intervals.

• Of 36 patients who received the drug, more than 30 actually regressed over six weeks—a stunning finding, since treatments for atherosclerosis had always been aimed at slowing down progression and actual regression was never thought possible.

• Both Cleveland Clinic and Esperion agreed that the revolutionary results should not be revealed to anyone until they got picked up by JAMA and the New England Journal of Medicine. Even Mr. Newton remained unaware of the study results in order to ensure that the information was not compromised.

• News of the results of the trial, published in JAMA in November 2003, hit the cardiovascular community, ushering in a new, revolutionary perspective on heart disease and atherosclerosis treatment.

• Dr. Nissen believes that administering ApoA-1 Milano followed by conventional maintenance therapy for atherosclerosis can eventually revolutionize treatment and dramatically reduce mortality associated with heart disease.

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Seen and Heard at the Summit:Interview with Steve Nissen, MD, Department of Cardiovascular Medicine, Cleveland Clinic

Dr. Nissen is one of the most outspoken proponents of truly independent research in drug trials. He spoke with MD Net Guide and shared his views on conflict of interest and the danger it poses.

MDNG: Is there a problem with financial conflicts of interest in today’s clinical trials?

SN: I have a simple rule: I will not accept any consultant fees or honoraria from any company for which I do research. I think that one of the reasons why people will trust in these results (of the ApoA-1 Milano trials) is that they know we are independent. The reason a company turns to an independent institution that has a reputation for integrity is that it helps the company, because people weren’t questioning the validity of our data.

MDNG: Do you think that this problem is getting worse?

SN: This is a serious problem. I’m actually going to be lecturing at the Council of Science Editors—it’s all the editors of the major journals—and we’re going to be talking about this, and we’re going to try to put in place improved safeguards to try to protect the integrity of the data. Esperion, in this case, went the extra mile. Actually having the CEO and the board not even know what the data showed was really pretty amazing.

MDNG: How has the cardiology community’s collective opinion of the definition of financial conflict of interest changed recently?

SN: Oh, it’s getting tougher and tighter. There’s no question that people are increasingly recognizing that there’s a problem with conflict of interest. I think we need to do better. I think we need standards that are much more rigid. I think that, in order for this to work, both the companies and the investigators have to come together on this.

MDNG: In what ways has the increasingly common phenomenon of researchers with a financial stake in the products they are testing affected the healthcare industry?

SN: It creates an environment in which people, including me, have a certain skepticism until we know whether the data were really generated in a way that has the highest level of integrity. So, if everyone had complete faith that there was no conflict of interest, then I think therapies could potentially move forward more quickly. My first reaction when something seems too good to be true is to question it. And I knew that I was up against that with ApoA-1 Milano, because it was almost a too-good-to-be-true result. That’s why I recommended to the company to shield the data.

MDNG: Do you think that there are enough rigorous clinical trials testing devices in the cardiology field?

SN: I think the device industry trials are generally poorly run. I think the financial conflict of interest problem is much worse in the device industry.

MDNG: What’s your opinion about the recent push for a public clinical trial registry? Who do you think should run this?

SN: I think it’s a good idea, but it’s not even close to being sufficient. It really isn’t even that big of an advance. In my view, it’s not nearly enough. And the problem with it is, knowing that a trial exists, all this does is protect against failure to publish negative results. It doesn’t really address the conflict of interest issue; it only addresses the suppression of results issue.

Guy J. Lebeau, MD, Group Chairman, Johnson & Johnson, and President, Cordis

Speeding Cardiovascular Innovation in an Uncertain Environment: A Case Study

Innovation requires a company or institution be “ambidextrous;” it must focus on incremental, substantial, and transformational innovation

Overview:

Dr. Lebeau explained the crucial issues and critical questions that a biotech company needs to address in order to accelerate innovation in an uncertain environment. He drew on several examples of innovative developments within Johnson & Johnson and Cordis.

Key Points:

• The key considerations that a company needs to take into account, according to Dr. Lebeau, are:

• Determining which model the company, group, or hospital belongs to (eg, a market-focused developer, a “big bet” researcher or developer, a technology developer, a market creator, or a technology acquirer)

• Determining whether an immediate crisis exists

• Questioning where the company should focus:

Change in perception

Change in expectation

New knowledge

Industry, market change

• Creating the right environment—giving people the freedom to create

Sense of urgency

Recognition of threat

Stay focused

Less formal

• Forming a transparent partnership—between group, company, or institution

• If current trends continue, by 2010, the need for percutaneous coronary intervention is going to increase at twice the rate of the number of interventional cardiologists.

• There is a “talent pool crisis”—the number of people in interventional cardiology or engineering fields between the ages of 35-44 years old is decreasing steadily as foreign-born professionals are leaving the US to return to their home countries. Currently, 33% of US doctors are 55 years or older and approaching retirement age. There is likely going to be a scarcity of talent in the US.

• To be successful in innovation, a company, group, or institution needs to, according to Dr. Lebeau, “be ambidextrous;” it needs to focus on three different types of innovation at the same time to have a diversified pipeline, including incremental inno-vation (using technology to improve upon an existing product), substantial innovation (using technology to create a new kind of product), and transformational innovation (going outside the company to find the technology to create a new product).

• 5% of researchers are driving 95% of innovation in this country

• The top 15 medical devices introduced in the last 10 years were invented by physicians, adopting available technology in 86% of cases.

• The key principles for ensuring a successful partnership are aligning your interests, sharing in the excitement, accepting information sharing, and the establishment of a centralized, visible control.

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A Policy Environment that Encourages Medical Innovation

Ronald Dollens, President and CEO, Guidant

“We’ve got to bring some competition to healthcare. Right now it’s all directed as a zero-sum game. It’s got to be able to be directed as a positive-sum game.”

Overview:

Mr. Dollens, who will complete a decade-long term as President and CEO of Guidant upon his retirement at the end of 2004, discussed the significant impact that innovation and technology have had on the health delivery process, the factors that contribute to the escalating cost of healthcare, and the roles that both government and private employers play in addressing these challenges.

Key Points:

• Guidant, a corporation with revenues of nearly $4 billion, netted $780 million in 2003 and has spent $500 million on product development.

• Health policy in the US has “incredible global implications,” both economically, and in the therapies that are available. “The US is financing the innovation process to the world.”

• Where the US ranks in infant mortality and life expectancy is “not where we would like it to be, but we do have the best healthcare in the world.” However, “disparities do exist in terms of access and coverage, and social behaviors exist to fall lower on list.”

• From 1980 to 2000, the mortality rate decreased by 16%, disability rates fell by 25%, hospital stays were reduced by 56%, and life expectancy increased by 3.2 years. Mortality rates in stroke patients were down by almost one-third, and overall cancer survival rates were three-times higher than 30 years prior.

• “Innovation across the whole delivery process of health has been constructive and should be encouraged.”

• As far as the growth of medical technology is concerned, the ability to attract investment of financial capital, “which then attracts human capital, the only source of creativity and ingenuity,” and direct it toward health, is crucial.

• With 12% of sales being spent on R&D, the two main sources of financial capital are the risk capital community (which spends almost $2 billion a year) and contributions from private, small companies.

• An estimated 43 million people are uninsured, which costs hospitals up to $24 billion. “They’re delivering care, but in an uncompensated manner.” About 80% of the uninsured are in working households.

• “The other 20% are falling between the cracks. We need a better outreach program to ensure that insurance is available to them. Employers have been surveyed and are willing to pay one third of the bill. We believe individuals are also willing to participate.”

• “Employers have to get out of the mode of paying a certain percentage of employee health plans without discriminating on which plans are delivering health the most efficiently.”

• Information is key for consumers to understand quality, outcomes, and costs.

• “We’ve got to bring some competition to healthcare. Right now it’s all directed as a zero-sum game. It’s got to be able to be directed as a positive-sum game.”

• “Don’t blame consumers for what has not happened in healthcare around choices. We have not given them any information. We have kept them blind. They do not know anything about quality, they do not know anything about cost, and they know very little about outcomes, because we have not been willing to share that information with them. That’s going to have to be one of the first steps.”

• “Health policy will determine whether patients have access to novel, innovative therapies as we go forward. And I don’t know that there’s a much greater mission in front of us.”

Interview with Ronald Dollens, CEO, Guidant

MDNG: Can you tell us about some of the innovations Guidant is developing that incorporate some of the new technologies that weren’t available 10 years ago?

RD: It’s really interesting, because of the 12 therapies we’re involved in, pacemakers for slow heart beats is the only therapy that was there [10 years ago], and there have been great advancements in that. If you think about where we are in terms of the newest therapies, we have these implantable defibrillators that will, if a patient is going into sudden cardiac death, resuscitate them, but at the same time, be able to pace left ventricular for patients in heart failure so that they cannot only increase their functionality but decrease their mortality rate, and the clinical trials have been able to show that. We think drug-eluting stents are going to be hugely important and, as [was discussed] at this conference, the emphasis is around vulnerable plaque where there’s a new concept on how heart attacks even happen. We think that stent technology or being able to deliver drugs locally along those lesions could be hugely important. So, we see that as the next big thing.

MDNG: What distinguishes Guidant from other medical device developers in terms of research and development?

RD: I think it’s our ability to iterate [that] at any point in time, 60% of Guidant sales are products that are less than 12 months old. We’ve always shown the ability to bring a new product to the market each year. So, to be able to continue to make advances, we think, probably stands out as one of our greatest competitive threats.

MDNG: From pharmaceuticals to medical devices, the industry of cardiovascular disease treatment has made great strides in recent years in terms of being able to manage and prevent heart conditions. How have these advancements affected the many patients who suffer from heart conditions?

RD: With cardiovascular disease, interestingly, mortality has declined substantially. And it’s not just medical technology. We think that angioplasty and stents and pacemakers and implantable defibrillators are all part of that. But pharmaceuticals are a huge part of that as well as clinicians [gaining a better] understanding of patient care. So, there’s been a process of innovation around the therapy. Some of it’s the device piece, some of it’s the pharmaceutical piece, and some is the patient-interaction piece. I think that the challenge will be—especially as people are concerned with obesity and specifically diabetes with that obesity—that there is a chance for us to use the progress we’ve made to date.

MDNG: More and more patients are using the Internet to supple-ment the information and advice they obtain from physician visits. Do you feel that the Internet serves as a useful tool for patients who use implantable devices?

RD: Patients use the Internet in a variety of ways. We have it available for patients and their families to try to understand, probably in better detail, some of the diseases they have. Studies have shown that when they’re interacting with the clinician, sometimes they’re thinking about things other than what the clinician is saying. I think that to have [the Internet] available to patients, everyone is just going to be so much more well-informed. I try to use this analogy: how many women today who get diagnosed with breast cancer are going to participate in the decision of how they’re going to be treated? I would say that’s a huge number. And the same goes for men with prostate cancer. How many of them do you think will participate in that decision of how they are going to be treated? The Internet’s going to be a big piece of that, where that information flow happens. It’ll be the first stop for patients. I think it is one of the real opportunities we have for patient-consumer delivery of healthcare. And [Guidant is] even talking about, and should launch next year, or even in the fourth quarter, the ability for our implanted devices to be able to have information transferred through the Internet to the clinician, and potentially, to patients.

Lessons in Innovation:

A Case Study in Heart Failure

William A. Hawkins, III,

President and COO, Medtronic

The value of biomedical innovation to the US equals

the value of innovation in all other sectors of the American economy combined.

Overview:

Mr. Hawkins reviewed facts and statistics about heart failure, discussed the risks that come with bringing a device from conception to post-approval, and explained the risks that come into play in the real world, illustrating key points by referring to the examples of several technologies that have or will play a major role in Medtronic’s heart failure journey.

Key Points:

• Two key factors that must be managed to ensure that innovation continues in the biomedical industry are tremendous risk and constructive collaboration.

• With heart failure currently an epidemic in the US, many entrepreneurs and big device companies are compelled to seek better ways of managing heart failure patients, such as cardiac resynchronization therapy, implantable defibrillators, left ventricular assist devices, and totally implantable artificial hearts.

• Not only must implanted devices be effective, they must be effective for years in a very hostile environment the human body.

• Results of the SCD-HeFT trial of 2,521 patients show unequivocally that people with heart failure live longer when they receive an implantable defibrillator, with a significant 23.6% reduction in mortality; the study also showed that amiodarone had no benefit over placebo in reducing rates of sudden cardiac death. The risk that results would be unfavorable at trial start was amplified by the fact that the device used—though state-of-the-art at trial start—was four generations removed by trial completion.

• “Our ability to innovate and manage risk is possible only through close collaboration with multiple stakeholders: physicians, the FDA, CMS, and other payers… In fact, almost every medical device on the market is the result of appropriate collaboration with practicing clinicians.”

• Through the MIRACLE trial, cardiac resynchronization therapy was shown to improve quality of life for heart failure patients. With the clinicians who brought CRT to reality through this trial, the FDA contributed tremendously by expediting the review and approval process (final study results submitted February 2001, approved by late August 2001),

• Collaboration that occurs after a device is approved and reimbursed is critical to successful patient outcomes and therapy adoption, such as involving clinicians in designing and implementing training and education tools for peers.

• Real-time monitoring of a patient’s status is a critical component of effective disease management, enabling clinicians to more quickly and accurately diagnose and treat changes in health status, improving outcomes and, overall, reducing costs in the long term.

Show #: 189761

Slide #: 0

www.mshow.com

Bruce Lytle MD, Chairman, Department of Thoracic & Cardiovascular Surgery, The Cleveland Clinic Foundation

The State of Cardiac Surgery

There is a dawning recognition [in the profession] of the need for the development of and involvement with multiple technologies.

Overview:

Dr. Lytle briefly reviewed the history of cardiac surgery and the way that those in the field look at the future as an introduction to a panel that described, in more detail, some of the interactions that they have had with the device industry and with their respective companies.

Key Points:

• “The types of surgery I do today are not going away, but there’s no question that the advent of multiple, potentially less-invasive technologies is going to affect what cardiac surgeons do, what we call a cardiac surgeon, how they behave, how they’re trained, and how we all fit together.”

• “The government has been spotty at best about funding innovation directly; the NIH tends not to like to fund things that directly affect patient care.

• With coronary bypass surgery came the “industrial era of cardiac surgery (past 30 years),” which had a massive economic imperative, led to modification of known devices and operations, decreased risk and improved long-term outcomes, funded the construction of the medical infrastructure, and decreased medical R & D because of reluctance to tamper with an operation that worked well most of the time.

• Cardiac surgery today is a smaller industry with a focus on less invasive procedures, most particularly percutaneous transvascular procedures involving coronary angioplasty.

• “Of all technologies developed, none have made the long-term outcomes any better, but they have made the procedure-related risks less in some cases, and certainly the procedure-related inconveniences a lot less, which has been what the focus is on for most multiple technologies.”

• Factors that limit technology include: inability to work well enough (it must be great), too expensive to develop and test, too limited a role in the market, training in use of technology too difficult or too slow (becomes more of a problem with more complex technology), enabling technologies not available (a big problem with robotics), technology is too expensive to use clinically, too much risk to the industry, and, especially to the surgeon using a new device, and small centers.

Show #: 189761

Slide #: 0 (after William Hawkins)

www.mshow.com

Surgical Innovation in Action

Panel Discusion Moderated by Bruce W. Lytle, MD,

Marc Gilinov, MD, CCF,Dave Drachman, CEO, AtriCure, Nick Smedia, MD, CCF, Richard Lunsford, CEO, Acorn Cardiovascular, Charles McIntosh, MD, CTO, Cook Group, Roy K. Greenberg, MD

Marc Gilinov, MD, CCF, Surgical Director, Center for Atrial Fibrillation, The Cleveland Clinic Foundation

Overview:

Dr. Gilinov described the clinical problems faced in his interaction with the world leader in the surgical treatment of the titular topic, AtriCure. The speaker also reviewed the basics of atrial

fibrillation (AF) and explained the past, present, and future of treatment for

this condition.

Key Points:

• Cardiac surgeons want to ablate AF because it is common (2.3 million in US), dangerous, and costly, and because ablation is now easy and successful through interaction with industry.

• The prevalence of AF is concentrated in people in their 60s, 70s, and 80s; the older a person is, the more likely an experienced stroke is from a heart rhythm problem.

• People with AF have a three-to-five-fold increased risk of stroke and a two-fold increased risk of mortality, experience side-effects from their medications, and cost society about $9,300 per year per person.

• In the past, the only option to treat was surgery: the Maze Procedure.New devices introduced in 2001 have led to a 40-fold increase in treating atrial fibrillation at the Cleveland Clinic.

• Most (89%) people with atrial fibrillation who undergo open-heart surgery end up in the OR for other reasons. “The next potential frontier is to get the people with isolated or lone atrial fibrillation to come and see a heart surgeon.”

• “We are on the way to developing endoscopic and truly minimally invasive approaches based upon technological innovation. Tthis will enable us to have a truly new paradigm for atrial fibrilla-tion cure.”

Dave Drachman, President and CEO, AtriCure

Overview:

Mr. Drachman outlined some of the steps being taken together with the Cleveland Clinic to create a future in which truly minimally invasive procedures are available.

Key Points:

• AtriCure has developed a tool kit of products that can be used in a video-assisted, endoscopic, off pump, bilateral, pulmonary vein isolation procedure with left atrial appendage exclusion for the treatment of lone atrial fibrillation. A tool was developed by AtriCure that passes through a 5mm endoscopic puncture site in the sixth intercostal space, under the left atrial pedicle and through the pericardial reflections, mobilizing the pulmonary veins and preparing the anatomy for an ablation device. It is exchanged with the ablation device, which uses jaws placed high up on the atrial cuff to capture as much atrial muscle as possible. The jaws are clamped, and seconds later, the tissue is fully ablated. The device creates an electrical line of conduction block between the pulmonary vein and the atrium.

• Another device uses the same puncture site and is maneuvered over the left atrial appendage, where a clip is deployed at the base, mechanically isolating the appendage from the atrium; this minimizes any risk of stroke associated with atrial fibrillation.

Nick Smedira, MD, CCF, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation

Overview:

Dr. Smedira described the Acorn Cardiac Support Device and lessons learned in one of two randomized surgical trials of the treatment of patients with very advanced heart failure.

Key Points:

• The trial discussed utilized a simple mesh placed around the heart with the idea that it could provide ventricular support to reduce wall stress and myocardial stress and promote myocardial reverse remodeling or at least halt the progression of the disease and stabilize the patient at a reasonable functional class so their quality of life is preserved.

• “If you have far-advanced heart failure, the likelihood of you being alive at two years is about 10%.”

Richard Lunsford, President and CEO, Acorn Cardiovascular, Inc.

Overview:

Mr. Lunsford gave his perspective on and shared his experiences with the Acorn trial.

Key Points:

• “This idea of multi-therapies coming together to start to solve heart failure that includes drug therapies and interaction between the heart failure cardiologists and the surgeon and the EP is very real. That is going to be the team of the future.”

• In the trial, site selection was key; the sites must understand the challenges of new therapy through extensive collaboration, provide input on trial design and data needed, give advice on acquisition of data, help in patient selection, and so on.

• New studies may require a steering committee, consisting of cardiologists, surgeons, researchers, a data and safety monitoring board, and a citizen efficiency review committee.

Charles McIntosh, MD, Chief Technology Officer, Cook Group

Overview:

Dr. McIntosh quickly reviewed key

facts and statistics regarding aortic aneurysms as an introduction to Dr. Greenberg’s presentation.

Key Points:

• Aortic aneurysms are the 17th leading cause of death (15,000/year).

• There are three interventional treatment devices currently available: AneuRx, approved in 1999, Excluder, approved in 2002, and Zenith, approved in 2003. All are limited to bifurcated systems, and they are incapable of accommodating complex anatomy.

Roy K. Greenberg, MD

Overview:

Dr. Greenberg shared the vision of many in his field that the entire aorta ultimately becomes the domain of the interventionalist, along with his views on the development of endographs.

Key Points:

• "Ultimately, we want to decrease morbidity and mortality, and we want to diminish the length of stay, remove that loss of independence that’s associated with open surgical repair and the long-term physical dysfunction."

• This vision requires shared resources among companies and hospitals. The clinical initiatives desired have to follow various product development protocol, but "we’ve brought this into practice through the use of Interventional Device Exemption studies" that allow initial implants to be done in the US. Sharing resources allows for device assessment on high-risk patients, but it mandates that the physicians who are involved have a very complete understanding of the device, because there is no clinical support for it. "This can only occur when the physician is initially involved in the device development."

• There’s a development paradigm: there’s a concept, which results in an engineering design, which results in animal and preclinical studie